The broad objectives of this project are to clarify the ontogenic and adaptive mechanisms which play a role in maturation of liver functions involving plasma membranes and microsomal membranes, namely biliary transport and secretory processes, and the conjugation of endogenous and exogenous substrates such as bilirubin and p-nitrophenol. Since these functions are intimately related to structural and compositional aspects of membranes, which in turn are profoundly influenced by cellular replication, and differentiation of surface receptors, an exploration of structure-function relationships in cell surface and microsomal membranes of mature, immature and neoplastic liver cells is planned. Specifically, developmental changes in membrane fluidity, measured by fluorescence polarization, will be correlated with membrane lipid composition, marker enzyme activity, and developmental acquisition of receptors for bile acids. Secondly, studies of bilirubin metabolism will concentrate on questions of clinical importance, such as elucidation of the effects of phototherapy on the kinetics, distribution, and biliary elimination of bilirubin, studies of the role of drug-brain interaction on uptake of bilirubin metabolism. Bile salt metabolism in infants with hepatic and biliary disorders will be investigated with non-hazardous stable isotope methods. These studies may clarify the mode of action of therapeutic agents and their effects on alternate metabolic pathways such as sulfation of primary bile acids. Collectively, these studies should yield new information about fundamental aspects of liver structure and function, and provide data useful in treatment of hepatobiliary disorders in infants.